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British Journal of Haematology Feb 2023Numerous studies have shown peculiar morphological anomalies in COVID-19 patients' smears. We searched all the peer-reviewed scientific publications that explicitly... (Review)
Review
Numerous studies have shown peculiar morphological anomalies in COVID-19 patients' smears. We searched all the peer-reviewed scientific publications that explicitly reference the cytomorphological alterations on peripheral blood smears of patients with COVID-19. We extracted data from sixty-five publications (case reports, patient group studies, reviews, and erythrocyte morphology studies). The results show that frequent alterations concern the morphology of lymphocytes (large lymphocytes with weakly basophilic cytoplasm, plasmacytoid lymphocytes, large granular lymphocytes). Neutrophils display abnormal nuclei and cytoplasm in a distinctive cytomorphological picture. Besides a left shift in maturation, granulations can be increased (toxic type) or decreased with areas of basophilia. Nuclei are often hyposegmented (pseudo-Pelger-Huёt anomaly). Apoptotic or pycnotic cells are not uncommon. Monocytes typically have a large cytoplasm loaded with heterogeneous and coalescing vacuoles. Platelets show large and giant shapes. The presence of erythrocyte fragments and schistocytes is especially evident in the forms of COVID-19 that are associated with thrombotic microangiopathies. Such atypia of blood cells reflects the generalized activation in severe COVID-19, which has been demonstrated with immunophenotypic, molecular, genetic, and functional methods. Neutrophils, in particular, are involved in the pathophysiology of hyperinflammation with cytokine storm, which characterizes the most unfavorable evolution.
Topics: Humans; COVID-19; Pelger-Huet Anomaly; Neutrophils; Monocytes; Killer Cells, Natural
PubMed: 36203344
DOI: 10.1111/bjh.18489 -
Head and Neck Pathology Dec 2020We present the historical review and current state of the histopathological classifications and terminology of laryngeal precursor lesions. Attention to recent genetic... (Review)
Review
We present the historical review and current state of the histopathological classifications and terminology of laryngeal precursor lesions. Attention to recent genetic findings is also presented; although in need of additional confirmation, these raise possibility for early detection of patients at risk of dysplasia progression. Although a number of identified genetic alterations with a promising diagnostic and prognostic value are emerging, none of the known genetic alterations can be currently implemented in clinical practice as a completely reliable diagnostic and/or prognostic marker. Regarding the terminology of precursor lesions, dysplasia remains the most frequently used term, but squamous intraepithelial lesion can be used as a synonym as well. Histological findings, in spite of certain degree of subjectivity, remain at present the most reliable method for an accurate diagnosis. The current 2017 WHO classification seems to successfully stratify risk of malignant progression, with a significantly different risk of malignant progression between low-grade dysplasia and high-grade dysplasia. In case of pronounced architectural disorders, severe cellular and nuclear atypias, and an increased number of mitoses, also atypical form, the high-grade dysplasia and carcinoma in situ can be separated. The Slovenian tertiary centers have a policy of surgical removal of high-grade SILs and life-long close follow-up. Radiotherapy is reserved for more pronounced intraepithelial lesions classified as carcinoma in situ and invasive cancer. Such a distinction can facilitate clinical decision to use radiotherapy if complete surgical removal is not possible.
Topics: Humans; Laryngeal Diseases; Larynx; Precancerous Conditions
PubMed: 32141027
DOI: 10.1007/s12105-020-01149-9 -
Current Oncology (Toronto, Ont.) Aug 2022Columnar cell lesions (CCLs) of the breast comprise a spectrum of morphologic alterations of the terminal duct lobular unit involving variably dilated and enlarged acini... (Review)
Review
Columnar cell lesions (CCLs) of the breast comprise a spectrum of morphologic alterations of the terminal duct lobular unit involving variably dilated and enlarged acini lined by columnar epithelial cells. The World Health Organization currently classifies CCLs without atypia as columnar cell change (CCC) and columnar cell hyperplasia (CCH), whereas flat epithelial atypia (FEA) is a unifying term encompassing both CCC and CCH with cytologic atypia. CCLs have been increasingly recognized in stereotactic core needle biopsies (CNBs) performed for the assessment of calcifications. CCLs are believed to represent the earliest non-obligate precursor of low-grade invasive breast carcinomas as they share molecular alterations and often coexist with entities in the low-grade breast neoplasia pathway. Despite this association, however, the risk of progression of CCLs to invasive breast carcinoma appears low and may not exceed that of concurrent proliferative lesions. As the reported upgrade rates of pure CCL/FEA when identified as the most advanced high-risk lesion on CNB vary widely, the management of FEA diagnosed on CNB remains controversial. This review will include a historical overview of CCLs and will examine histologic diagnostic criteria, molecular alterations, prognosis and issues related to upgrade rates and clinical management.
Topics: Breast; Breast Neoplasms; Epithelial Cells; Female; Humans; Hyperplasia
PubMed: 36005185
DOI: 10.3390/curroncol29080447 -
Asian Pacific Journal of Cancer... 2016Central neurocytomas are rare neuronal neoplasms with a favorable prognosis. They are typically located in the lateral ventricles of the brain and mostly histologically... (Review)
Review
BACKGROUND
Central neurocytomas are rare neuronal neoplasms with a favorable prognosis. They are typically located in the lateral ventricles of the brain and mostly histologically correspond to WHO grade II with a Mib 1 labelling index of <2%. Similar tumors located in the cerebral hemispheres and spinal cord, for example, are called "extraventricular neurocytomas". A few tumors histologically show atypia, mitoses, vascular proliferation and/or necrosis and a Mib 1 index >2 % and are designated as "atypical neurocytomas.
AIM
The aim of our study was to describe the common as well as unusual morphologic features and the role of various immunohistochemical stains in the diagnosis of these rare tumors.
MATERIALS AND METHODS
We retrieved and reviewed 35 cases diagnosed between 2001 and 2015.
RESULTS
Sixty percent of patients were males, and the mean age was 26 years. 31 cases (88.6%) were intraventricular and 4(11.4%) were extraventricular. Histologically, 6 cases (17.1%) were compatible with "atypical neurocytomas". All cases showed the classic morphology comprising nests and sheets of uniform, round cells with uniform round to oval nuclei with finely speckled chromatin and perinuclear cytoplasmic clearing (halos). All cases also showed delicate, fibrillary, neuropil-like matrices. Other common histologic features included capillary-sized blood vessels in a branching pattern in 57.1%, foci of calcification in 34.3% and perivascular pseudorosettes in 20%. Rare findings included Homer- Wright or true rosettes in 8.6% and ganglioid cells in 2.9%. Synaptophysin was the most consistent and valuable marker, being positive in almost all cases. GFAP positivity in tumor cells was seen in 25.7% of cases. Follow up was available in 13 patients. Of these 9 had histologically typical and 4 had atypical tumors. Only 1 (with an atypical neurocytoma) died, probably due to complications of surgery within one month, while 12 (including 3 with atypical neurocytomas) remained alive. Recurrence developed in 1 of these 12 patients (histologically consistent with typical morphology) almost 9 years after surgery. Only 4 patients, including 2 with atypical tumors, received postoperative radiotherapy, all with surgery in 2010 or later. Overall, prognosis was excellent with prolonged, recurrence free survival and most patients, even without receiving radiation therapy, were alive and well for many years, even a decade or more after surgery, without developing any recurrence, indicating the benign nature of these neoplasms.
Topics: Adolescent; Adult; Biomarkers, Tumor; Brain Neoplasms; Child; Female; Follow-Up Studies; Humans; Immunoenzyme Techniques; Male; Middle Aged; Neoplasm Staging; Neurocytoma; Pakistan; Prognosis; Young Adult
PubMed: 27039806
DOI: 10.7314/apjcp.2016.17.3.1565 -
Archives of Pathology & Laboratory... Oct 2014We review the morphology and differential diagnoses of pseudocarcinomatous hyperplasia of the bladder, using a study case to illustrate the discussion.... (Review)
Review
We review the morphology and differential diagnoses of pseudocarcinomatous hyperplasia of the bladder, using a study case to illustrate the discussion. Pseudocarcinomatous hyperplasia is a rare, reactive response to an ischemic insult, classically to radiation therapy, and consists of proliferative, pseudoinfiltrative urothelial nests within the stroma. The presence of background radiation therapy-related changes, such as numerous dilated thrombosed vessels, reactive-appearing endothelial and stromal cells, edema, and hemorrhage, can provide clues to the diagnosis. The main differential diagnoses include invasive urothelial carcinoma and the nested variant of urothelial carcinoma; morphologic features, such as the presence or absence of background therapy-related changes and the architecture and the cytologic atypia of the nests, can help distinguish between pseudocarcinomatous hyperplasia and urothelial carcinoma.
Topics: Adenocarcinoma; Carcinoma; Cystitis; Diagnosis, Differential; Hematuria; Humans; Hyperplasia; Male; Middle Aged; Prostatic Neoplasms; Radiation Injuries; Urinary Bladder; Urinary Bladder Neoplasms; Urothelium
PubMed: 25268187
DOI: 10.5858/arpa.2014-0311-CC -
Cancers Jan 2023In cytologic analysis of lung nodules, specimens classified as atypia cannot be definitively diagnosed as benign or malignant. Atypia patients are typically subject to...
In cytologic analysis of lung nodules, specimens classified as atypia cannot be definitively diagnosed as benign or malignant. Atypia patients are typically subject to additional procedures to obtain repeat samples, thus delaying diagnosis. We evaluate morphologic categories predictive of lung cancer in atypia patients. This retrospective study stratified patients evaluated for primary lung nodules based on cytologic diagnoses. Atypia patients were further stratified based on the most severe verbiage used to describe the atypical cytology. Logistic regressions and receiver operator characteristic curves were performed. Of 129 patients with cytologic atypia, 62.8% later had cytologically or histologically confirmed lung cancer and 37.2% had benign respiratory processes. Atypia severity significantly predicted final diagnosis even while controlling for pack years and modified Herder score (p = 0.012). Pack years, atypia severity, and modified Herder score predicted final diagnosis independently and while adjusting for covariates (all p < 0.001). This model generated a significantly improved area under the curve compared to pack years, atypia severity, and modified Herder score (all p < 0.001) alone. Patients with severe atypia may benefit from repeat sampling for cytologic confirmation within one month due to high likelihood of malignancy, while those with milder atypia may be followed clinically.
PubMed: 36672346
DOI: 10.3390/cancers15020397 -
Diagnostic Cytopathology Jan 2021The rate of malignancy (ROM) in thyroid fine needle aspirations (FNA) classified under "atypia of undetermined significance (AUS)/follicular lesion of undetermined...
An institutional experience: A retrospective analysis of the effect of transitioning from follicular lesion of undetermined significance to atypia of undetermined significance with subclassified atypia on interobserver concordance, rates of neoplasia, and rates of malignancy.
INTRODUCTION
The rate of malignancy (ROM) in thyroid fine needle aspirations (FNA) classified under "atypia of undetermined significance (AUS)/follicular lesion of undetermined significance (FLUS), including Hürthle cell type (HLUS)" category of The Bethesda system for reporting thyroid cytopathology (TBSRTC) in literature is highly variable. The 2018 TBSRTC was updated to note a preferred categorization of AUS cases into subcategories. This study evaluates the impact of AUS subclassification on rates of neoplasia (RON), rates of malignancy (ROM), and cytopathologist (CP) concordance.
METHODS
93 thyroid FNAs previously diagnosed as FLUS or HLUS from January 1, 2013 to December 31, 2014 with subsequent surgical resection were identified. Four CPs reclassified these cases using TBSRTC AUS subcategories of follicular cells with architectural and/or cytologic atypia, predominantly Hürthle cells, and atypical lymphocytes. RON and ROM were calculated for each diagnostic subcategory for each CP.
RESULTS
The original RON and ROM for FLUS cases were 31.4% and 15.1% and were 77.8% and 22.2% for HLUS cases. 10.8% of cases showed diagnostic concordance amongst the four CPs. The most frequently utilized subcategory was architectural atypia. RON ranges for architectural atypia, cytologic atypia, architectural and cytologic atypia, and predominantly Hürthle cells were 28.1% to 35.7%, 0% to 33.3%, 35.3% to 66.7%, and 57.1% to 87.5%. The range of ROM was 13.9% to 16.7%, 0% to 33%, 0% to 42.9%, and 0% to 25%, respectively.
CONCLUSION
RON for AUS predominantly Hürthle cells subcategory was higher than previously reported, which may indicate use for tailored patient management pathways. AUS subclassification can result in significant interobserver variability. Therefore, institutions may consider consensus/quality control sessions to optimize diagnostic concordance.
Topics: Adenocarcinoma, Follicular; Biopsy, Fine-Needle; Carcinoma, Papillary; Female; Humans; Male; Observer Variation; Retrospective Studies; Thyroid Gland; Thyroid Neoplasms; Thyroid Nodule
PubMed: 32936526
DOI: 10.1002/dc.24611 -
Cancer Science May 2021Uterine leiomyosarcoma (LMS) is a rare but deadly disease. Due to poor understanding of the molecular and genetic causes of the disease, the diagnosis of LMS has been...
Uterine leiomyosarcoma (LMS) is a rare but deadly disease. Due to poor understanding of the molecular and genetic causes of the disease, the diagnosis of LMS has been based primarily on histology. Nuclear atypia is one of hallmarks in LMS, however, it also occurs in 2 clinically benign variants, including smooth muscle tumors with fumarate hydratase alteration (SMT-FH) and leiomyoma with bizarre nuclei (LM-BN). In addition to nuclear atypia, many well recognized biomarkers used for LMS are also frequently overexpressed in LM-BN, and the histogenesis and molecular natures for LM-BN and LMS remain largely unknown. To characterize the molecular profiling of LMS, SMT-FH, and LM-BN, we performed integrated comprehensive genomic profiling including whole-genome sequencing (WGS) and RNA sequencing and genomic microarray analyses to assess genome-wide copy number alterations (CNAs) and immunohistochemistry (IHC) in all 3 tumor types. We found that both LM-BN and LMS showed genomic instability and harbored extensive CNAs throughout the whole genome. By contrast, the SMT-FH presented its characteristic 1q43-44 deletions in all cases tested, with minimal CNAs in the rest of genomic regions. Further analyses revealed that LMS and LM-BN groups showed similar patterns of CNAs that are tended to cluster together and separated from the SMT-FH group. The integrated molecular profiling enabled the detection of novel and traditional biomarkers and showed excellent discrimination between LM-BN and LMS. Our study suggests that LM-BN, despite having similar nuclear atypia to SMT-FH, showed similar genomic instability but distinct genomic alterations with its malignant counterpart of LMS. The integrated molecular profiling is of clinical importance in characterizing these rare uterine smooth muscle tumors.
Topics: Adult; Biomarkers, Tumor; Cell Nucleus; Female; Fumarate Hydratase; Gene Deletion; Gene Dosage; Gene Expression Profiling; Humans; Leiomyoma; Leiomyosarcoma; Middle Aged; Muscle, Smooth; Necrosis; Principal Component Analysis; Sequence Analysis, RNA; Tissue Array Analysis; Uterine Neoplasms
PubMed: 33338329
DOI: 10.1111/cas.14775 -
Gastrointestinal Tumors Jun 2021Gastrointestinal stromal tumor (GIST) of the ampulla of Vater is a rare occurrence. To the best of our knowledge, there has been no published review on this rare tumor... (Review)
Review
BACKGROUND
Gastrointestinal stromal tumor (GIST) of the ampulla of Vater is a rare occurrence. To the best of our knowledge, there has been no published review on this rare tumor in the English literature so far.
SUMMARY
In this review, we will discuss all the reported details of the published cases, including demography, clinical presentation, imaging, gross pathology and histopathology, immunohistochemical findings, treatment modalities, and outcome of cases with the diagnosis GIST from the ampulla of Vater in the last 20 years.
KEY MESSAGE
Twenty-five cases of GIST in the ampulla of Vater have been reported in the last 20 years in the English literature. GIST in the ampulla of Vater are usually small tumors (<5 cm) in middle-age patients. The majority of the patients present with lower GI bleeding and abdominal pain. Imaging findings are not characteristic, and most of the patients without biopsy and with no histologic diagnosis were operated with the primary impression of adenocarcinoma, neuroendocrine tumor, and GIST. Perioperative tissue biopsy has been accurate in <70% of the cases. The majority of the reported cases of GISTs in the ampulla of Vater have been low risk with spindle-cell morphology, low mitotic figures, and minimal atypia; reactive for C-KIT and DOG-1; and nonreactive for SMA, desmin, and S100. In the majority of the cases, duodenectomy with or without Whipple's operation has been performed, and most of the cases showed good prognosis.
PubMed: 34307307
DOI: 10.1159/000514613 -
Archives of Pathology & Laboratory... Apr 2008Flat epithelial atypia is a presumably neoplastic alteration of terminal duct-lobular units that is characterized by the replacement of the native luminal epithelium by... (Review)
Review
Flat epithelial atypia is a presumably neoplastic alteration of terminal duct-lobular units that is characterized by the replacement of the native luminal epithelium by ductal cells demonstrating low-grade cytologic atypia. The atypical cells maintain a "flat" pattern of growth without evidence of architectural atypicality. Morphologic, immunohistochemical, and molecular investigations support that flat epithelial atypia represents an early step in the evolution of low-grade ductal carcinomas. It is frequently seen in association with atypical ductal hyperplasia, low-grade ductal carcinoma in situ, invasive tubular carcinoma, and lobular neoplasia. The risk for subsequent breast carcinoma remains to be defined, but flat epithelial atypia likely represents a nonobligate precursor with an extended time course to progression. Certain benign alterations may superficially mimic its appearance; careful attention to cytologic and architectural characteristics can help one distinguish these unrelated entities from flat epithelial atypia.
Topics: Biopsy; Breast; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Diagnosis, Differential; Epithelial Cells; Female; Humans; Hyperplasia; Pathology
PubMed: 18384213
DOI: 10.5858/2008-132-615-FEAOTB